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How is pancreatic cancer diagnosed?

If a person has signs and symptoms that might be caused by pancreatic cancer, certain exams and tests will be done to find the cause. If cancer is found, further tests will then be done to help determine the extent (stage) of the cancer.

Medical history and physical exam

Your doctor will ask about your medical history to check for any pancreatic cancer risk factors, and to learn more about any symptoms you are having, such as pain, changes in appetite, weight loss, and tiredness.

A thorough physical exam will focus mostly on your abdomen (belly) to check for any masses or fluid buildup. Cancers that block the bile duct may cause the gallbladder to enlarge, which can sometimes be felt on physical exam. Pancreatic cancer may spread to the liver, causing it to enlarge. Your skin and the whites of your eyes will be checked for jaundice (yellowing).

Pancreatic cancer can also spread to lymph nodes above the collarbone and other locations. These areas will be looked at carefully for lumps or swelling that might mean cancer spread.

If the results of the exam are abnormal, your doctor will probably order tests to help find the problem. You might also be referred to a gastroenterologist (a doctor who treats digestive system diseases) for further tests and treatment.

Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests might be done for a number of reasons both before and after a diagnosis of pancreatic cancer, including:

To look for suspicious areas that might be cancer

To learn if and how far cancer has spread

To help determine if treatment is working

To look for signs of cancer coming back after treatment

Computed tomography (CT) scan

The CT scan uses x-rays to produce detailed cross-sectional images of your body. CT scans are often used to diagnose pancreatic cancer because they can show the pancreas fairly clearly. They can also help show if cancer has spread to organs near the pancreas, as well as to lymph nodes and distant organs. A CT scan can help determine if surgery might be a good treatment option.

A CT scanner has been described as a large donut, with a narrow table that slides in and out of the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken. Instead of taking one picture, like a standard x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body.

Before the test, you might be asked to drink 1 to 2 pints of a liquid called oralcontrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You might also receive an IV line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures such as blood vessels in your body.

The injection can cause some flushing (redness and warm feeling). Some people are allergic to the dye and get hives or, rarely, have more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have ever had a reaction to any contrast material used for x-rays.

If your doctor suspects you might have pancreatic cancer, you may have one set of CT scans of your abdomen taken before you get IV contrast. Other sets of scans may then be taken over the next several minutes as the contrast passes through the pancreas and other parts of the body. These sets of scans together are known as a multiphase CT scan or a pancreatic protocol CT scan.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle into a suspected pancreatic tumor. But if a needle biopsy is needed, most doctors prefer to use endoscopic ultrasound (described below) to guide the needle into place.

For this procedure, you remain on the CT scanning table while the doctor advances a biopsy needle through the skin and toward the tumor. CT scans are repeated until the needle is within the mass. A needle biopsy sample is then removed to be looked at under a microscope.

Magnetic resonance imaging (MRI)

MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a detailed image of parts of the body. A contrast material might be injected just as with CT scans, but this is used less often.

Most doctors prefer to look at the pancreas with CT scans, but an MRI can also be done.

Special types of MRI scans can also be used in people who might have pancreatic cancer:

MR cholangiopancreatography (MRCP), which can be used to look at the pancreatic and bile ducts, is described below in the section on cholangiopancreatography.

MR angiography (MRA), which looks at blood vessels, is mentioned below in the section on angiography.

MRI scans take longer than CT scans – often up to an hour – and are a little more uncomfortable. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you might find disturbing. Some places give you headphones or earplugs to help block this noise out.

Ultrasound

Ultrasound tests use sound waves to create images of organs such as the pancreas.

Abdominal ultrasound: For this test, a wand-shaped probe called a transducer is moved over the skin of the abdomen. It gives off sound waves and detects the echoes as they bounce off organs. The pattern of echoes is processed by a computer to produce an image on a screen. The echoes made by most pancreatic tumors differ from those of normal pancreas tissue. Different echo patterns can help doctors tell some types of pancreatic tumors from one another.

If it’s not clear what might be causing a person’s abdominal symptoms, an ultrasound might be the first test done because it is easy to do and it doesn’t expose a person to radiation. But if signs and symptoms are more likely to be caused by pancreatic cancer, a CT scan is often more useful for looking at the pancreas than an ultrasound.

Ultrasound is also commonly used to look at the liver, and may be used if someone has symptoms (like jaundice) that point to a liver problem.

Endoscopic ultrasound (EUS): This test is more accurate than abdominal ultrasound and can be very helpful in diagnosing pancreatic cancer. This test is done with a small ultrasound probe on the tip of an endoscope — a thin, flexible tube that doctors use to look at the inside of the digestive tract.

For this test, you will first be sedated (given medicine to make you sleepy). The probe is then passed through your mouth or nose, down through the esophagus and stomach, and into the first part of the small intestine. It is then pointed toward the pancreas, which is next to the small intestine. The probe on the tip of the endoscope can get very close to the pancreas, so this is a very good way to look at the pancreas. It is better than CT scans for spotting small tumors. If a tumor is seen, a small, hollow needle can be passed down the endoscope to get biopsy samples of it during this procedure.

Cholangiopancreatography

A cholangiopancreatogram is an imaging test that looks at the pancreatic and bile ducts to see if they are blocked, narrowed, or dilated. These tests can help show if someone might have a pancreatic tumor that is blocking a duct. They can also be used to help plan surgery. The test can be done in different ways, each of which has pros and cons.

Endoscopic retrograde cholangiopancreatography (ERCP): For this test, an endoscope (a thin, flexible tube with a tiny video camera on the end) is passed down the throat, through the esophagus and stomach, and into the first part of the small intestine. This is usually done while you are sedated (given medicine to make you sleepy).

The doctor can see through the endoscope to find the ampulla of Vater (where the common bile duct empties into the small intestine). The doctor guides a catheter (a very small tube) through the tip of the endoscope and into the common bile duct. A small amount of dye (contrast material) is then injected into the common bile duct, and x-rays are taken. This dye outlines the bile and pancreatic ducts. The x-ray images can show narrowing or blockage in these ducts that might be due to pancreatic cancer. The doctor doing this test can also put a small brush through the tube to remove cells for a biopsy (to view under a microscope to see whether or not they look like cancer).

ERCP can also be used to place a stent (small tube) into a bile or pancreatic duct to keep it open if a nearby tumor is pressing on it. This is described in more detail in the section on palliative surgery in the “Surgery for pancreatic cancer” section.

Magnetic resonance cholangiopancreatography (MRCP): This is a non-invasive way to look at the pancreatic and bile ducts using the same type of machine used for standard MRI scans. It does not require an infusion of a contrast agent and is not invasive, unlike ERCP. Because it is non-invasive, doctors often use MRCP if the purpose of the test is just to look at the pancreatic and bile ducts. But this test can’t be used to get biopsy samples of tumors or to place stents in ducts.

Percutaneous transhepatic cholangiography (PTC): In this procedure, the doctor places a thin, hollow needle through the skin of the belly and into a bile duct within the liver. A contrast dye is then injected through the needle, and x-rays are taken as it passes through the bile and pancreatic ducts. As with ERCP, this approach can also be used to take fluid or tissue samples or to place a stent into a duct to help keep it open. Because it is more invasive (and might cause more pain), PTC is not usually used unless ERCP has already been tried or can’t be done for some reason.

Somatostatin receptor scintigraphy (SRS)

This test, also known as OctreoScan, can be very helpful in diagnosing pancreatic neuroendocrine tumors (NETs). It uses a hormone-like substance called octreotide that is bound to a radioactive substance (indium-111). Octreotide attaches to proteins on the tumor cells of many NETs, but it is less helpful in finding insulinomas.

A small amount of this substance is injected into a vein. It travels through the blood and attaches to NETs. About 4 hours after the injection, a special camera can be used to show where the radioactivity has collected in the body. More scans may be done on the following few days as well.

This scan can help diagnose NETs, but it can also help decide on treatment. NETs that show up on SRS scans will often stop growing if treated with octreotide.

Positron emission tomography (PET) scan

For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. The amount of radioactivity used is very low and will pass out of the body over the next day or so. Because cancer cells in the body grow quickly, they absorb large amounts of the radioactive sugar. After about an hour, you will be moved onto a table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

This test is sometimes used to look for spread from exocrine pancreatic cancers, but because NETs grow slowly, they do not show up well on PET scans.

Special machines can do both a PET and CT scan at the same time (known as a PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan. This test can help determine the stage (extent) of the cancer. It might be especially useful for spotting exocrine cancer that has spread beyond the pancreas and wouldn’t be treatable by surgery.

Angiography

This is an x-ray test that looks at blood vessels. A small amount of contrast material is injected into an artery to outline the blood vessels, and then x-rays are taken.

Angiography can show if blood flow in a particular area is blocked or compressed by a tumor. It can also show any abnormal blood vessels (feeding the cancer) in the area. This test can be useful in finding out if a pancreatic cancer has grown through the walls of certain blood vessels. Mainly, it helps surgeons decide if the cancer can be removed completely without damaging vital blood vessels and helps them plan the operation.

Angiography can also be used to look for pancreatic NETs that are too small to be seen on other imaging tests. These tumors cause the body to make more blood vessels to “feed” the tumor. These extra blood vessels can be seen on angiography.

X-ray angiography can be an uncomfortable procedure because the doctor has to put a small catheter into the artery leading to the pancreas. Usually the catheter is put into an artery in your inner thigh and threaded up to the pancreas. A local anesthetic is often used to numb the area before inserting the catheter. Then the dye is injected quickly to outline all the vessels while the x-rays are being taken.

Angiography can also be done with a CT scanner (CT angiography) or an MRI scanner (MR angiography). These techniques are now used more often because they can give information about the blood vessels in or near the pancreas without the need for a catheter in the artery. You might still need an IV line so that a contrast dye can be injected into the bloodstream during the imaging.

Blood tests

Several types of blood tests can be used to help diagnose pancreatic cancer or to help determine treatment options if it is found.

Blood tests for exocrine pancreatic cancers

Liver function tests: Jaundice (yellowing of the skin and eyes) is often one of the first signs of pancreatic cancer, but it can have many causes other than cancer. Doctors often get blood tests to assess liver function in people with jaundice to help determine its cause.

For example, blood tests that look at levels of different kinds of bilirubin (a chemical made by the liver) can help tell whether a patient’s jaundice is caused by disease in the liver itself or by a blockage of bile flow (from a gallstone, a tumor, or other disease).

Tumor markers: Tumor markers are substances that can sometimes be found in the blood when cancer is present. Two tumor markers may be helpful in pancreatic cancer:

CA 19-9 is a substance often released into the blood by exocrine pancreatic cancer cells, although it often can’t be detected until the cancer is already advanced.

Carcinoembryonic antigen (CEA) is another tumor marker that might help find advanced pancreatic cancer in some people, but it is not used as often as CA 19-9.

Neither of these tumor marker tests is accurate enough to tell for sure whether or not someone has pancreatic cancer. Levels of these tumor markers are not high in all people with pancreatic cancer, and some people who don’t have pancreatic cancer might have high levels of these markers for other reasons. Still, these tests can sometimes be helpful, along with other tests, in figuring out if someone has cancer.

In people already known to have pancreatic cancer and who have high CA19-9 or CEA levels, these levels can be followed over time to help tell how well treatment is working. If all of the cancer has been removed, these tests can also be done to look for the cancer coming back.

Other blood tests: Other tests can help evaluate a person’s general health (such as kidney and bone marrow function). These tests can help determine if they’ll be able to withstand the stress of a major operation.

Blood tests for pancreatic neuroendocrine tumors

Blood tests looking at the levels of certain pancreatic hormones can often help diagnose pancreatic neuroendocrine tumors (NETs).

For insulinomas, insulin, glucose, and C-peptide levels are measured while the patient is fasting (not eating or drinking). (C peptide is a by-product of insulin production). Blood is drawn every 6 to 8 hours until the patient starts having symptoms of low blood sugar. The diagnosis of an insulinoma is made when there is low blood glucose with high levels of insulin and C-peptide.

Other pancreatic hormones, such as gastrin, glucagon, somatostatin, pancreatic polypeptide, and VIP (vasoactive intestinal peptide) can be measured in blood to help diagnose pancreatic NETs. Measuring the level of a substance called chromogranin A (CgA) can be very helpful. This level goes up in most cases of pancreatic NETs — even tumors that don’t make excess hormones (non-functioning tumors).

People with heartburn or ulcers who are taking medicines known as proton pump inhibitors, such as omeprazole (Prilosec®), esomeprazole (Nexium®), lansoprazole (Prevacid®), often need to stop taking them for a week before having these tests. This is because these medicines can falsely raise gastrin and CgA levels.

Measurement of gastrin levels is most useful when combined with a test that measures the amount of acid in the stomach. This is because low acid levels can lead to high gastrin levels. When a gastrinoma is present, high gastrin levels are seen along with high acid levels.

Carcinoid tumors: For carcinoids, a blood test may be done to look for serotonin, which is made by many of these tumors. The body breaks serotonin down into 5-hydroxyindoleactic acid (5-HIAA) and releases it into the urine. A test commonly used to look for carcinoid syndrome measures the levels of 5-HIAA in a urine sample collected over 24 hours. This test can help diagnose many (but not all) carcinoid tumors.

Sometimes, the tumors do not make much serotonin, but they do make its precursor, 5-HTP, which can be converted to serotonin in the urine. In patients with these tumors, the blood serotonin level may be normal, but the urine levels of serotonin and 5-HTP are high.

Eating foods that contain a lot of serotonin can raise 5-HIAA levels in the urine. Such foods include bananas, plantains, kiwi, certain nuts, avocado, tomatoes, and eggplant. Medicines, including cough syrup and acetaminophen (Tylenol), can also affect the results. These substances should be avoided before urine and blood testing for carcinoids.

Other common tests to look for carcinoids include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin. As noted above, medicines called proton-pump inhibitors, which lower stomach acid, can raise CgA and gastrin levels even in people without carcinoid tumors. If you take one of these medicines, talk to your doctor about what you need to avoid before having these blood tests.

Depending on where the tumor might be located and the patient’s symptoms, doctors might do other blood tests as well.

Biopsy

A person’s medical history, physical exam, and imaging test results may strongly suggest pancreatic cancer, but usually the only way to be sure is to remove a small sample of tumor and look at it under the microscope. This procedure is called a biopsy. Biopsies can be done in different ways.

Percutaneous (through the skin) biopsy: For this test, a doctor inserts a thin, hollow needle through the skin over the abdomen and into the pancreas to remove a small piece of a tumor. This is known as a fine needle aspiration (FNA). The doctor guides the needle into place using images from ultrasound or CT scans.

Endoscopic biopsy: Doctors can also biopsy a tumor during an endoscopy. The doctor passes an endoscope (a thin, flexible, tube with a small video camera on the end) down the throat and into the small intestine near the pancreas. At this point, the doctor can either use endoscopic ultrasound (EUS) to pass a needle into the tumor or endoscopic retrograde cholangiopancreatography (ERCP) to remove cells from the bile or pancreatic ducts. These tests are described in more detail above. You will be sedated (made sleepy) for these tests, but general anesthesia (being put into a deep sleep) is not usually needed. Major side effects from these types of biopsies are rare.

Surgical biopsy: Surgical biopsies are now done less often than in the past. They can be useful if the surgeon is concerned the cancer has spread beyond the pancreas and wants to look at (and possibly biopsy) other organs in the abdomen.

The most common way to do a surgical biopsy is to use laparoscopy (sometimes called keyhole surgery). You will be sedated or asleep for this procedure. The surgeon makes several small incisions (cuts) in the abdomen and inserts small telescope-like instruments. One of these has a small video camera on the end to let the surgeon see inside the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy samples of abnormal areas.

In the past, surgeons often used a laparotomy (a large incision through the skin into the wall of the abdomen) to examine internal organs and take biopsies. But this type of surgery requires a longer recovery and is now rarely used.

Some people might not need a biopsy

Rarely, the doctor might not do a biopsy on someone who has a tumor in the pancreas if imaging tests show the tumor is very likely to be cancer and if it looks like surgery can remove all of it. Instead, the doctor will proceed with surgery, at which time the tumor cells can be looked at to confirm the diagnosis. If the doctor finds during surgery that the cancer has spread too far to be removed completely, only a sample of the cancer may be removed to confirm the diagnosis, and the rest of the planned operation will be stopped.

If treatment (such as chemotherapy or radiation) is planned before surgery, a biopsy is needed first to be sure of the diagnosis.